Capture and removal of biomolecules from body fluids using partial molecular imprints

Abstract

The invention provides methods and devices for the capture and removal of target biomolecules from a patient's body fluid, particularly blood or a blood component, using a partial imprint material. The partial imprint material is composed of a matrix composition having partial imprint cavities that correspond to a segment of a target biomolecule but which are capable of removing the entire target biomolecule from the body fluid. The method can be implemented by removing a volume of a patient's body fluid, e.g., blood, bringing the body fluid or a component thereof into contact with the partial imprint material under conditions effective to capture the target biomolecule, and returning the body fluid to the patient. A modified dialysis or apheresis device can be used in which the body fluid is removed, continuously passed through a circuit containing the partial imprint material, and re-introduced into the patient's body following treatment.

1 . A method for selectively removing a target biomolecule from a body fluid of a patient, comprising: 
 passing at least one component of the body fluid through a partial imprint material comprising a matrix composition having a plurality of partial imprint cavities, wherein each partial imprint cavity is of a template molecule that corresponds to a segment of the biomolecule, under conditions in which the partial imprint cavities capture the target biomolecule, thereby depleting the body fluid of the biomolecule.    
   
   
       2 . The method of  claim 1 , wherein the body fluid is selected from blood, lymph fluid, and spinal fluid.  
   
   
       3 . A method for treating a patient by removing a target biomolecule from the patient's blood, comprising: 
 (a) continuously removing a flow of blood from the patient;    (b) continuously separating the removed blood into a plasma component and a cellular component;    (c) continuously passing at least one of the plasma component and the cellular component through a partial imprint material comprising a matrix composition having a plurality of partial imprint cavities, wherein each partial imprint cavity is of a template molecule that corresponds to a segment of the target biomolecule, under conditions in which the partial imprint cavities capture the biomolecule, thereby producing a treated plasma component and/or a treated cellular component; and    (d) continuously returning the treated plasma component and/or the treated cellular component a to the patient's body.    
   
   
       4 . The method of  claim 3 , wherein the biomolecule is a peptidic molecule.  
   
   
       5 . The method of  claim 4 , wherein the biomolecule is an oligopeptide, polypeptide, or protein.  
   
   
       6 . The method of  claim 5 , wherein the biomolecule is a polypeptide.  
   
   
       7 . The method of  claim 6 , wherein the template molecule is an oligopeptide corresponding to a contiguous sequence of the polypeptide.  
   
   
       8 . The method of  claim 7 , wherein the oligopeptide is in the range of about 3 to about 30 amino acids in length.  
   
   
       9 . The method of  claim 8 , wherein the oligopeptide is in the range of about 4 to about 14 amino acids in length.  
   
   
       10 . The method of  claim 9 , wherein the oligopeptide is in the range of about 4 to about 7 amino acids in length.  
   
   
       11 . The method of  claim 7 , wherein the contiguous sequence of the polypeptide is at the C-terminus.  
   
   
       12 . The method of  claim 3 , wherein the target biomolecule is α-synuclein.  
   
   
       13 . The method of  claim 3 , wherein the target biomolecule is an amyloid peptide.  
   
   
       14 . The method of  claim 13 , wherein the biomolecule is selected from the group consisting of amyloid and amyloid-β.  
   
   
       15 . The method of  claim 14 , wherein the biomolecule is amyloid-β.  
   
   
       16 . The method of  claim 3 , wherein the biomolecule is prion protein (PrP).  
   
   
       17 . The method of  claim 16 , wherein the biomolecule is a PrP fragment.  
   
   
       18 . The method of  claim 16 , wherein the biomolecule is PrP96-111.  
   
   
       19 . The method of  claim 3 , wherein the biomolecule is an autoantibody.  
   
   
       20 . The method of  claim 2 , wherein the biomolecule is nucleotidic.  
   
   
       21 . The method of  claim 20 , wherein the template molecule is an oligonucleotide.  
   
   
       22 . The method of  claim 3 , wherein the biomolecule is selected from lipids, lipoproteins, and lipopolysaccharides.  
   
   
       23 . The method of  claim 3 , wherein the biomolecule is a polysaccharide.  
   
   
       24 . The method of  claim 3 , wherein the biomolecule is immunoreactive.  
   
   
       25 . The method of  claim 3 , wherein the biomolecule is present on the surface of a cell, and capture of the biomolecule by a partial imprint cavity results in capture of the cell.  
   
   
       26 . The method of  claim 3 , wherein the matrix composition comprises at least two different partial imprint cavities, wherein each of the at least two different partial imprint cavities corresponds to a different target biomolecule.  
   
   
       27 . The method of  claim 3 , wherein the plasma component is passed through the partial imprint material.  
   
   
       28 . The method of  claim 3 , wherein the cellular component is passed through the partial imprint material.  
   
   
       29 . An apparatus for treating a patient by removing target biomolecules from the patient's blood, comprising: 
 means for removing a continuous flow of blood from the patient;    means for continuously separating the removed blood into a plasma component and a cellular component;    means for continuously passing at least one of the plasma component and the cellular component through a partial imprint material comprising a matrix composition having a plurality of partial imprint cavities, wherein each partial imprint cavity is of a template molecule that corresponds to a segment of the target biomolecule, under conditions in which the partial imprint cavities capture the biomolecule, to thereby produce a treated plasma component and/or a treated cellular component; and    means for returning the treated plasma component and/or the treated cellular component to the patient.    
   
   
       30 . The apparatus of  claim 29 , wherein the biomolecule is a peptidic molecule.  
   
   
       31 . The apparatus of  claim 30 , wherein the biomolecule is an oligopeptide, polypeptide, or protein.  
   
   
       32 . The apparatus of  claim 31 , wherein the biomolecule is a polypeptide.  
   
   
       33 . The apparatus of  claim 32 , wherein the template molecule is an oligopeptide corresponding to a contiguous sequence of the polypeptide.  
   
   
       34 . The apparatus of  claim 33 , wherein the oligopeptide is in the range of about 3 to about 30 amino acids in length.  
   
   
       35 . The apparatus of  claim 34 , wherein the oligopeptide is in the range of about 4 to about 14 amino acids in length.  
   
   
       36 . The apparatus of  claim 35 , wherein the oligopeptide is in the range of about 4 to about 7 amino acids in length.  
   
   
       37 . The apparatus of  claim 33 , wherein the contiguous sequence of the polypeptide is at the C-terminus.  
   
   
       38 . The apparatus of  claim 30 , wherein the target biomolecule is α-synuclein.  
   
   
       39 . The apparatus of  claim 30 , wherein the target biomolecule is an amyloid peptide.  
   
   
       40 . The apparatus of  claim 39 , wherein the biomolecule is selected from the group consisting of amyloid and amyloid-β.  
   
   
       41 . The apparatus of  claim 40 , wherein the biomolecule is amyloid-β.  
   
   
       42 . The apparatus of  claim 30 , wherein the biomolecule is prion protein (PrP).  
   
   
       43 . The apparatus of  claim 42 , wherein the biomolecule is a PrP fragment.  
   
   
       44 . The apparatus of  claim 30 , wherein the biomolecule is an autoantibody.  
   
   
       45 . The apparatus of  claim 29 , wherein the biomolecule is nucleotidic.  
   
   
       46 . The apparatus of  claim 29 , wherein the template molecule is an oligonucleotide.  
   
   
       47 . The apparatus of  claim 29 , wherein the biomolecule is selected from lipids, lipoproteins, and lipopolysaccharides.  
   
   
       48 . The apparatus of  claim 29 , wherein the biomolecule is a polysaccharide.  
   
   
       49 . The apparatus of  claim 29 , wherein the biomolecule is immunoreactive.  
   
   
       50 . The apparatus of  claim 29 , wherein the matrix composition comprises at least two different partial imprint cavities, wherein each of the at least two different partial imprint cavities corresponds to a different target biomolecule.  
   
   
       51 . A method for treating a patient suffering from an autoimmune disease, 
 (a) continuously removing a flow of blood from the patient;    (b) continuously separating the removed blood into a plasma component and a cellular component;    (c) continuously passing at least one of the plasma component and the cellular component through a partial imprint material comprising a matrix composition having a plurality of partial imprint cavities, wherein each partial imprint cavity is of a template molecule that corresponds to a segment of an autoantibody associated with the autoimmune disease, under conditions in which the partial imprint cavities capture the autoantibody, thereby producing a treated plasma component and/or a treated cellular component; and    (d) continuously returning the treated plasma component and/or the treated cellular component to the patient's body.    
   
   
       52 . The method of  claim 51 , wherein the autoimmune disease is selected from Addison's disease, Crohn's disease, insulin-dependent diabetes mellitus (IDDM), Grave's disease, Hashimoto's thyroiditis, myasthenia gravis, autoimmune gastritis, pernicious anemia, multiple sclerosis, Sjögren's syndrome, autoimmune hemolytic anemia, thrombocytopenia purpura, psoriasis, pemphigus vulgarus, bullous pemphigoid, epidermolysis bullosa acquisita, cutaneous lupus erythematosis, systemic lupus erythematosis (SLE), scleroderma, rheumatoid arthritis (RA), and antiphospholipid/cofactor syndromes.  
   
   
       53 . A method for treating a patient suffering from a disease or disorder associated with the presence or an excess of a target biomolecule, comprising: 
 a) continuously removing a flow of blood from the patient;    (b) continuously separating the removed blood into a plasma component and a cellular component;    (c) continuously passing at least one of the plasma component and the cellular component through a partial imprint material comprising a matrix composition having a plurality of partial imprint cavities, wherein each partial imprint cavity is of a template molecule that corresponds to a segment of the target biomolecule, under conditions in which the partial imprint cavities capture the target biomolecule, thereby producing a treated plasma component and/or a treated cellular component; and    (d) continuously returning the treated plasma component and/or the treated cellular component to the patient's body.